Developing Biomarkers for Fibromyalgia (Biomarkers)

The hypothesis of this study is that biological markers are present in the body that are good indicators of chronic pain. Eligible participants will be assessed at baseline and after receiving a series of acupuncture or "sham" acupuncture (something that resembles, but is not, active acupuncture) sessions. If the subject qualifies for the investigators' research and are subsequently enrolled in this study, they will be randomly assigned (like the flip of a coin) to one of these two groups. Acupuncture, as previously shown by this group, leads to improvements in both clinical and evoked pain associated with fibromyalgia. The study involves two magnetic resonance imaging (MRI) brain scans, one at the beginning and one at the end of the study. Another optional portion of the study would involve 2 PET (positron emission tomography) scans of the subject's brain, one at the beginning and one at the end of the study; this type of scan allows us to get more specific information about the subject's brain function during an acupuncture session.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Other: Traditional Acupuncture; Other: Sham Treatment

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan, Chronic Pain and Fatigue Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion Criteria for Fibromyalgia Volunteers:

• Has met American College of Rheumatology (1990) criteria for the diagnosis of fibromyalgia for at least 1 year
• Chronic pain more than 50% of days
• Willing to limit introduction of any new medications or treatments for fibromyalgia during the study
• Able to attend study visits up to three times weekly
• Right-handed
• Be capable of giving written informed consent

Inclusion Criteria for Healthy Volunteers:

• Willing to refrain from alcohol intake for 48 hours prior to brain scans
• Be right handed
• Be capable of giving written informed consent

PET Inclusion Criteria:

• Willing to refrain from alcohol intake 48 hours prior to brain scans
• Capable of giving written consent

Exclusion Criteria:

Exclusion Criteria for Fibromyalgia Volunteers:

• Knowledge that could prevent "blinding" of the participant to the study interventions (including previous acupuncture treatment)
• Presence of a known coagulation abnormality, thrombocytopenia, or bleeding diathesis that may preclude the safe use of acupuncture
• Autoimmune or inflammatory disease (in addition to fibromyalgia) that causes pain (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease)
• Daily use of narcotic pain-relievers
• History of substance abuse
• Simultaneous participation in other therapeutic trials
• Pregnant or breastfeeding
• Current severe psychiatric illness (e.g., schizophrenia, major depression with suicidal ideation)
• Condition that may make exposure to fMRI medically inadvisable
• Any condition that may prevent satisfactory completion of the study protocol

Exclusion for Healthy Volunteers:

• Autoimmune or inflammatory disease (in addition to fibromyalgia) that causes pain (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease)
• Having met the ACR criteria for FM
• Simultaneous participation in other therapeutic trials
• Pregnant or breastfeeding
• Current severe psychiatric illness (e.g., schizophrenia, major depression with suicidal ideation)
• Condition that may make exposure to fMRI medically inadvisable
• Any condition that may prevent satisfactory completion of the study protocol

PET Exclusion Criteria:

• Meets any of the fMRI exclusion criteria
• Current major depression
• Condition that may make exposure to PET medically inadvisable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Traditional Acupuncture; Acupuncture sites will be used for active intervention.	Other: Traditional Acupuncture; Fibromyalgia subjects will be randomized to receive 9 acupuncture treatments over the course of four weeks. Subjects enrolled in the study may have 1) only fMRI or 2) fMRI scans and PET scans, depending on their eligibility criteria.
SHAM_COMPARATOR: Sham Treatment; Sham acupuncture is used.	Other: Sham Treatment; Fibromyalgia subjects will be randomized to receive 9 sham treatments over the course of four weeks. Subjects enrolled in the study may have 1) only fMRI or 2) fMRI scans and PET scans, depending on their eligibility criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
fMRI signal	pre treatment - week 1
PET signal	pre treatment - week 1
H-MRS Glutamate	pre treatment - week 1
fMRI signal	post treatment - week 5
PET signal	post treatment - week 5
H-MRS - Glutamate	post treatment - week 5

Secondary Outcome Measures

Outcome Measure	Time Frame
Pain	pre treatment - week 1
Pain	post treatment - week 5

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: United States Department of Defense; The Dana Foundation
• Investigators: Principal Investigator: Richard Harris, Ph.D., Univeristy of Michigan, Chronic Pain & Fatigue Research Center

Publications and helpful links

General Publications

• Harris RE, Zubieta JK, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage. 2009 Sep;47(3):1077-85. doi: 10.1016/j.neuroimage.2009.05.083. Epub 2009 Jun 6.
• Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 2008 Mar;58(3):903-7. doi: 10.1002/art.23223.
• Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007 Sep 12;27(37):10000-6. doi: 10.1523/JNEUROSCI.2849-07.2007.
• Harris RE, Sundgren PC, Craig AD, Kirshenbaum E, Sen A, Napadow V, Clauw DJ. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum. 2009 Oct;60(10):3146-52. doi: 10.1002/art.24849.
• Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010 Aug;62(8):2545-55. doi: 10.1002/art.27497.

Helpful Links

• University of Michigan Research Studies
• Chronic Pain and Fatigue Research Center

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: June 25, 2009
• First Submitted That Met QC Criteria: July 1, 2009
• First Posted (ESTIMATE): July 2, 2009

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Acupuncture; fMRI; Fibromyalgia; Biological marker; Healthy controls; Sham Acupuncture
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: Hum 00010061; F017513; Sponsor(DOD) W81XWH-07-20050